Profilin 1 is essential for retention and metabolism of mouse hematopoietic stem cells in bone marrow

Junke Zheng, Zhigang Lu, Fatih Kocabas, Ralph T. Böttcher, Mercedes Costell, Xunlei Kang, Xiaoye Liu, Ralph J DeBerardinis, Qianming Wang, Guo Qiang Chen, Hesham A Sadek, Chengcheng Zhang

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

How stem cells interact with the microenvironment to regulate their cell fates and metabolism is largely unknown. Here we demonstrated that the deletion of the cytoskeleton-modulating protein profilin 1 (pfn1) in hematopoietic stem cell (HSCs) led to bone marrow failure, loss of quiescence, and mobilization and apoptosis of HSCs in vivo. A switch from glycolysis to mitochondrial respiration with increased reactive oxygen species (ROS) level was also observed in HSCs on pfn1 deletion. Importantly, treatment of pfn1-deficient mice with the antioxidant N-acetyl-L-cysteine reversed the ROS level and loss of quiescence of HSCs, suggesting that the metabolism is mechanistically linked to the cell cycle quiescence of stem cells. The actin-binding and proline-binding activities of pfn1 are required for its function in HSCs. Our study provided evidence that pfn1 at least partially acts through the axis of pfn1/Gα13/EGR1 to regulate stem cell retention and metabolism in the bone marrow.

Original languageEnglish (US)
Pages (from-to)992-1001
Number of pages10
JournalBlood
Volume123
Issue number7
DOIs
StatePublished - Feb 13 2014

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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